An epidemiological survey of hepatitis C virus infection in Italian children in the decade 1990-1999.

BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.     

Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access((R)) GI Monitor assay on the UniCel((R)) DxI 800 Immunoassay System

Abstract Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access((R)) GI Monitor assay (Beckman Coulter) was evaluated on the UniCel((R)) DxI 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access((R)) GI Monitor and Elecsys CA19-9 (R=0.959, slope=1.004, intercept=+0.17). GI Monitor serum levels were low in healthy individuals (n=267, median=6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n=550, medians=5.8-13.4 kU/L, 95th percentiles=30.1-195.5kU/L) and even higher in individuals suffering from various cancers (n=995, medians=8.4-233.8 kU/L, 95th percentiles=53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access((R)) GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers. Clin Chem Lab Med 2008;46:600-11.     

Pediatric liver transplantation: the University of Padua experience

OBJECTIVE: The objective of this study was to analyze experience on pediatric liver transplantation (LT) between June 1993 and September 2006, including split liver transplantation (SLT), living donor liver transplantation (LDLT), and auxiliary partial orthotopic liver transplantation (APOLT). Furthermore, hepatocyte transplantation (HT) had a role in one patient with metabolic disease. METHODS: From November 1990 to September 2006, 657 LTs were performed including 63 pediatric LTs (9.6%) in 57 patients (32 boys and 25 girls). Six were retransplantations (9.5%). Thirty-two patients (57%) were younger than 5 years. The types of graft included the following: 26 whole organs (41%), 32 in situ split organs (51%), 4 reduced-size organs (6%), and 1 graft from a living donor (2%). Two patients received an APOLT, 4 patients received a combined kidney-liver transplantation (CKLT), and 1 patient received HT. Of the 63 pediatric LTs, 16 were behaved to be highly urgent (25%). RESULTS: Overall 1-, 3-, 5-, and 10-year patient survival rates were 82%, 82%, 78%, and 78%, respectively. Overall 1-, 3-, 5-, and 10-year graft survival rates were 76%, 76%, 72%, and 72%, respectively. In patients younger than 1 year, the 5-year survival rate was 100%. Perioperative mortality was 8.8%. Vascular complications occurred in 4 patients (6.3%). Six children required retransplantation due to primary nonfunction (PNF) in 4 cases (7%) and vascular thrombosis in 2 cases (3.5%). CONCLUSIONS: Cholestatic liver disease and age younger than 1 year were the best prognostic factors for excellent survival.     

Antiphospholipid syndrome in a child with trisomy 21: the relationship between anticardiolipin G antibodies and the von Willebrand factor.

A young child with trisomy 21 developed severe multiple arterial thromboses in a three-phase clinical course which proved fatal. The episodes were characterized by high levels of both IgG anticardiolipin antibodies and the von Willebrand factor. The data suggest that there is a relationship between these two elements and the clinical events which followed.     

Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.

BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.     

A new hip-knee-ankle-foot sling: kinematic comparison with a traditional ankle-foot orthosis

In this study, we performed a kinematic analysis of a new, low-cost sling for the lower limb, compared to a common ankle-foot orthosis (AFO). Gait with no orthosis, with the AFO, and with the new sling was analyzed in one hemiplegic subject. Both the AFO and the sling reduced the mean angle and ROM (range of movement) of the ankle and the vertical displacement of the center of mass. The sling, but not the AFO, restored the normal sequence heel-strike, forefoot contact of the affected side. The sling, but not the AFO, reduced the affected limb stance and stride duration, increased stride length, and improved walking speed. In conclusion, the proposed sling for the lower limb equally improved the affected ankle kinematics in contrast to the traditional AFO, and it also improved some gait variables in this hemiplegic subject.     

The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease

Background It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin. Methods Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5′ untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 wd patients in whom no mutations were detected in the ATP7B gene, 53 wd patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin. Results We  detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls. Conclusions These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.     

Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation

Crigler-Najjar syndrome types I and II (CN1 and CN2) are usually inherited as autosomal recessive conditions and are characterized by non-hemolytic unconjugated hyperbilirubinaemia. CN1 is the most severe form, associated with the absence of hepatic bilirubin-uridinediphosphoglucuronate glucuronosyltransferase (UGT1A1) activity. CN2 presents intermediate levels of hyperbilirubinaemia as a result of an incomplete deficiency of hepatic UGT1A1 activity. Here, we present the analysis of UGT1A1 gene in 31 unrelated Crigler-Najjar (CN) syndrome patients. This analysis allowed us to identify 22 mutations, 12 of which were not previously described, expanding the spectrum of known UGT1 mutations to 77. Novel mutations, considered pathogenic, including one nonsense mutation, two altered splice sites, one single base deletion and nine missense mutations were identified in coding exons of the UGT1A1gene and flanking introns. Several novel missense mutations localize in critical domain of UGT1A1 enzyme. In addition, the evaluation of Gilbert-type promoter of UGT1A1in Crigler-Najjar (CN) syndrome patients was performed. The polymorphisms of the promoter region can modify the UGT1A1 mutation phenotype. This study represents the molecular characterization of the largest cohort of Italian Crigler-Najjar Gilbert syndrome patients studied so far; increase the mutational spectrum of UGT1A1 allelic variants worldwide and provide a new insight useful for clinical diagnosis and genetic counseling.